【摘要】 目的辅助临床确诊1例婴儿神经轴索营养不良(infantile neuroaxonal dystrophy,INAD)家系,为患者家庭遗传咨询和产前诊断提供依据。方法收集患者临床资料,提取先证者及家系成员外周血基因组DNA,PCR扩增INAD致病基因PLA2G6编码序列并进行测序。对发现的突变位点在对照人群中进行验证及相关生物信息学分析。结果先证者表现为进行性智力发育及运动能力落后,头颅MRI显示小脑萎缩。测序结果发现患者PLA2G6基因存在复合性杂合突变,分别为父源性的c.668C>T(p.Pro223Leu)和母源性的c.1534T>A(p.Phe512Ile)突变,且二者在对照人群中未检测到。生物信息学分析显示两种突变均为致病性突变,可引起蛋白质二级结构和氨基酸亲水性改变。结论发现PLA2G6基因的新突变位点c.1534T>A,该突变可与已知致病突变c.668C>T共同导致常染色体隐性遗传病INAD的发生。更多还原

【Abstract】 Objective To provide assistance for clinical diagnosis of a family with infantile neuroaxonal dystrophy( INAD) and provide basis for the genetic counseling and prenatal diagnosis of INAD families. Methods The clinical information of the patient was collected. The genomic DNA was extracted from peripheral blood of the proband and other family members. The coding sequence of PLA2G6,a candidate gene of INAD,was amplified by polymerase chain reaction and the mutation was detected by direct sequencing. The novel mutations were validated in control population,and bioinformatics analysis suggested to in silico prediction. Results The intelligence development and motor ability of the patient were progressively retrograded and his head imaging information indicated cerebellar atrophy. Compound heterozygous mutations in PLA2G6 of the patient,i. e.,two mutations from the paternal c. 668 C > T mutation and maternal c. 1534 T > A mutation were identified,which could not be found in control population. The in silico prediction results suggested both the mutations were pathogenic to change the structure of protein and hydrophilicity of the amino acid. Conclusion A new mutation c. 1534 T > A in PLA2G6 gene was identified. The mutation may cooperate with the known pathogenic c. 668 C > T mutation to result in the autosomal recessive disorder of INAD.更多还原